DOVOBET

Main information

  • Trade name:
  • DOVOBET Ointment 50 + 0.5
  • Dosage:
  • 50 + 0.5
  • Pharmaceutical form:
  • Ointment
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOVOBET Ointment 50 + 0.5
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1659/018/001
  • Authorization date:
  • 08-10-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dovobet50microgram/g+0.5mg/gointment

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Calcipotriol50microgram/g(ashydrate),betamethasone0.5mg/g(asdipropionate).

Excipients:ContainsButylhydroxytoluene(E321)

Forafulllistofexcipients,seeSection6.1.

3PHARMACEUTICALFORM

Ointment.

ProductimportedfromtheUK

Off-whitetoyellow.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Topicaltreatmentofstableplaquepsoriasisvulgarisamenabletotopicaltherapyinadults.

4.2Posologyandmethodofadministration

Dovobetointmentshouldbeappliedtotheaffectedareaoncedaily.Therecommendedtreatmentperiodis4weeks.

ThereisexperiencewithrepeatedcoursesofDovobetupto52weeks.Ifitisnecessarytocontinueorrestarttreatment

after4weeks,treatmentshouldbecontinuedaftermedicalreviewandunderregularmedicalsupervision.

Whenusingcalcipotriolcontainingmedicinalproducts,themaximumdailydoseshouldnotexceed15g.Thebody

surfaceareatreatedwithcalcipotriolcontainingmedicinalproductsshouldnotexceed30%(seesection4.4).

SpecialPopulations

Renalandhepaticimpairment

ThesafetyandefficacyofDovobetointmentinpatientswithsevererenalinsufficiencyorseverehepaticdisordershave

notbeenevaluated.

Paediatricpopulation

ThesafetyandefficacyofDovobetointmentinchildrenbelow18yearshavenotbeenestablished.Nodataare

available.

MethodofAdministration

Dovobetointmentshouldbeappliedtotheaffectedarea.Inordertoachieveoptimaleffect,itisnotrecommendedto

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4.3Contraindications

Hypersensitivitytotheactivesubstancesortoanyoftheexcipients.

Dovobetointmentiscontraindicatedinerythrodermic,exfoliativeandpustularpsoriasis.

DuetothecontentofcalcipotriolDovobetiscontra-indicatedinpatientswithknowndisordersofcalciummetabolism.

Duetothecontentofcorticosteroid,Dovobetiscontraindicatedinthefollowingconditions:Viral(e.g.herpesor

varicella)lesionsoftheskin,fungalorbacterialskininfections,parasiticinfections,skinmanifestationsinrelationto

tuberculosisorsyphilis,perioraldermatitis,atrophicskin,striaeatrophicae,fragilityofskinveins,ichthyosis,acne

vulgaris,acnerosacea,rosacea,ulcers,wounds,perianalandgenitalpruritus.

4.4Specialwarningsandprecautionsforuse

Effectsonendocrinesystem

DovobetointmentcontainsastrongpotentgroupIII-Steroidandconcurrenttreatmentwithothersteroidsmustbe

avoided.Adversereactionsfoundinconnectionwithsystemiccorticosteroidtreatmentsuchasadrenocortical

suppressionorimpactonthemetaboliccontrolofdiabetesmellitusmayoccuralsoduringtopicalcorticosteroid

treatmentduetosystemicabsorption.

Applicationunderocclusivedressingsshouldbeavoidedsinceitincreasesthesystemicabsorptionofcorticosteroids.

Applicationonlargeareasofdamagedskinoronmucousmembranesorinskinfoldsshouldbeavoidedsinceit

increasesthesystemicabsorptionofcorticosteroids(seeSection4.8).

Inastudyinpatientswithbothextensivescalpandextensivebodypsoriasisusingacombinationofhighdosesof

Dovobetgel(scalpapplication)andhighdosesofDovobetointment(bodyapplication),5of32patientsshoweda

borderlinedecreaseincortisolresponsetoadrenocorticotropichormone(ACTH)challengeafter4weeksoftreatment

(seesection5.1)

Effectsoncalciummetabolism

Duetothecontentofcalcipotriol,hypercalcaemiamayoccurifthemaximumdailydose

(15g)isexceeded.Serumcalciumis,however,quicklynormalisedwhentreatmentisdiscontinued.Theriskof

hypercalcaemiaisminimalwhentherecommendationsrelevanttocalcipotriolarefollowed.Treatmentofmorethan

30%ofthebodysurfaceshouldbeavoided(seesection4.2).

Localadversereactions

Skinofthefaceandgenitalsareverysensitivetocorticosteroids.Themedicinalproductshouldnotbeusedinthese

areas.Thepatientmustbeinstructedincorrectuseofthemedicinalproducttoavoidapplicationandaccidentaltransfer

totheface,mouthandeyes.Handsmustbewashedaftereachapplicationtoavoidaccidentaltransfertotheseareas.

Concomitantskininfections

Whenlesionsbecomesecondarilyinfected,theyshouldbetreatedwithantimicrobiologicaltherapy.However,when

infectionworsens,treatmentwithcorticosteroidsshouldbestopped.

Discontinuationoftreatment

Whentreatingpsoriasiswithtopicalcorticosteroidstheremaybeariskofgeneralisedpustularpsoriasisorofrebound

effectswhendiscontinuingtreatment.Medicalsupervisionshouldthereforecontinueinthepost-treatmentperiod.

Long-termuse

Withlong-termusethereisanincreasedriskoflocalandsystemiccorticosteroidadversereactions.Thetreatment

shouldbediscontinuedincaseofadversereactionsrelatedtolong-termuseofcorticosteroids(seesection4.8).

Unevaluateduses

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ConcurrenttreatmentandUVexposure

Thereisnoexperiencefortheuseofthismedicinalproductonthescalp.Dovobetointmentforbodypsoriasislesions

hasbeenusedincombinationwithDovobetgelforscalppsoriasislesions,butthereisnoexperienceofcombinationof

Dovobetwithothertopicalanti-psoriaticproductsatthesametreatmentarea,otheranti-psoriaticmedicinalproducts

administeredsystemicallyorwithphototherapy.

DuringDovobetointmenttreatment,physiciansarerecommendedtoadvisepatientstolimitoravoidexcessive

exposuretoeithernaturalorartificiallight.TopicalcalcipotriolshouldbeusedwithUVRonlyifthephysicianand

patientconsiderthatthepotentialbenefitsoutweighthepotentialrisks(seesection5.3).

Dovobetointmentcontainsbutylhydroxytoluene(E321).Thismaycauselocalskinreactions(e.gcontactdermatitis),or

irritationtotheeyesandmucousmembranes.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Nointeractionstudieshavebeenperformed.

4.6Fertility,pregnancyandlactation

Pregnancy

TherearenoadequatedatafromtheuseofDovobetointmentinpregnantwomen.Studiesinanimalswith

glucocorticoidshaveshownreproductivetoxicity(seesection5.3),butanumberofepidemiologicalstudieshavenot

revealedcongenitalanomaliesamonginfantsborntowomentreatedwithcorticosteroidsduringpregnancy.The

potentialriskforhumansisuncertain.Therefore,duringpregnancy,Dovobetointmentshouldonlybeusedwhenthe

potentialbenefitjustifiesthepotentialrisk.

BreastfeedingBetamethasonepassesintobreastmilkbutriskofanadverseeffectontheinfantseemsunlikelywith

therapeuticdoses.Therearenodataontheexcretionofcalcipotriolinbreastmilk.Cautionshouldbeexercisedwhen

prescribingDovobetointmenttowomenwhobreastfeed.ThepatientshouldbeinstructednottouseDovobetointment

onthebreastwhenbreastfeeding.

Fertility

Studiesinratswithoraldosesofcalcipotriolorbetamethasonedipropionatedemonstratednoimpairmentofmaleand

femalefertility.

4.7Effectsonabilitytodriveandusemachines

Dovobethasnoornegligibleinfluenceontheabilitytodriveandtousemachines.

4.8Undesirableeffects

ThetrialprogrammeforDovobetointmenthassofarincludedmorethan2,500patientsandhasshownthat

approximately10%ofpatientscanbeexpectedtoexperienceanon-seriousundesirableeffect.

Thesereactionsareusuallymildandcovermainlyvariousskinreactionslikerash,pruritusandburningsensation.

Pustularpsoriasishasbeenreportedrarely.Reboundeffectafterendoftreatmenthasbeenreportedbutthefrequency

ofthisisnotknown.

BasedondatafromclinicaltrialsandpostmarketusethefollowingadversereactionsarelistedforDovobetointment.

TheadversereactionsarelistedbyMedDRASystemOrganClassandtheindividualadversereactionsarelisted

startingwiththemostfrequentlyreported.Withineachfrequencygrouping,theadversereactionsarelistedinorderof

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Thefollowingterminologieshavebeenusedinordertoclassifythefrequenciesofadversereactions:

Verycommon 1/10

Common 1/100to<1/10

Uncommon 1/1,000to<1/100

Rare 1/10,000to<1/1,000

Veryrare <1/10,000

Notknown(cannotbeestimatedfromtheavailabledata)

Generaldisordersandadministrationsiteconditions

Notknown:Reboundeffect–includedinsection4.4

Thefollowingadversereactionsareconsideredtoberelatedtothepharmacologicalclassesofcalcipotrioland

betamethasone,respectively.

Calcipotriol

adversereactionsincludeapplicationsitereactions,pruritus,skinirritation,burningandstingingsensation,dryskin,

erythema,rash,dermatitis,eczema,psoriasisaggravated,photosensitivityandhypersensitivityreactionsincludingvery

rarecasesofangioedemaandfacialoedema.

Systemiceffectsaftertopicalusemayappearveryrarelycausinghypercalcaemiaorhypercalciuria(seesection4.4)

Betamethasone(asdipropionate)

Localreactionscanoccuraftertopicaluse,especiallyduringprolongedapplication,includingskinatrophy,

telangiectasia,striae,folliculitis,hypertrichosis,perioraldermatitis,allergiccontactdermatitis,depigmentationand

colloidmilia.Whentreatingpsoriasistheremaybeariskofgeneralisedpustularpsoriasis.

Systemicreactionsduetotopicaluseofcorticosteroidsarerareinadults,howevertheycanbesevere.Adrenocortical

suppression,cataract,infections,impactonthemetaboliccontrolofdiabetesmellitusandincreaseofintra-ocular

pressurecanoccur,especiallyafterlongtermtreatment.Systemicreactionsoccurmorefrequentlywhenappliedunder

occlusion(plastic,skinfolds),whenappliedonlargeareasandduringlongtermtreatmentcf.Section4.4.

4.9Overdose

Useabovetherecommendeddosemaycauseelevatedserumcalciumwhichshouldrapidlysubsidewhentreatmentis

discontinued.Excessiveprolongeduseoftopicalcorticosteroidsmaysuppressthepituitary-adrenalfunctionsresulting

insecondaryadrenalinsufficiencywhichisusuallyreversible.Insuchcasessymptomatictreatmentisindicated.

Skinandsubcutaneoustissuedisorders

Common: Pruritus

Common: Rash

Common: Burningsensationofskin

Uncommon:Exacerbationofpsoriasis

Uncommon:Skinpainorirritation

Uncommon:Dermatitis

Uncommon:Erythema

Uncommon:Folliculitis

Uncommon:Applicationsitepigmentationchanges

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Ithasbeenreportedthatduetomisuseonepatientwithextensiveerythrodermicpsoriasistreatedwith240gof

Dovobetointmentweekly(correspondingtoadailydoseofapproximately34g)for5months(maximum

recommendeddose15gdaily)developedCushing’ssyndromeandpustularpsoriasisafterabruptlystoppingtreatment.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Antipsoriatics.Otherantipsoriaticsfortopicaluse,CalcipotriolcombinationsATCCode:

D05AX52

CalcipotriolisavitaminDanalogue.Invitrodatasuggeststhatcalcipotriolinducesdifferentiationandsuppresses

proliferationofkeratinocytes.Thisistheproposedbasisforitseffectinpsoriasis.

Likeothertopicalcorticosteroids,betamethasonedipropionatehasanti-inflammatory,antipruritic,vasoconstrictiveand

immunosuppressiveproperties,however,withoutcuringtheunderlyingcondition.Throughocclusiontheeffectcanbe

enhancedduetoincreasedpenetrationofthestratumcorneum(approximatelybyafactorof10).Theincidenceof

adverseeventswillincreasebecauseofthis.Themechanismoftheanti-inflammatoryactivityofthetopicalsteroids,in

general,isunclear.

Asafetystudyin634psoriasispatientshasinvestigatedrepeatedcoursesofDovobetointmentusedoncedailyas

required,eitheraloneoralternatingwithDovonex,forupto52weeks,comparedwithDovonexusedalonefor48

weeksafteraninitialcourseofDovobetointment.Adversedrugreactionswerereportedby21.7%ofthepatientsinthe

Dovobetgroup,29.6%intheDovobet/Dovonexalternatinggroupand37.9%intheDovonexgroup.Theadversedrug

reactionsthatwerereportedbymorethan2%ofthepatientsintheDovobetointmentgroupwerepruritus(5.8%)and

psoriasis(5.3%).Adverseeventsofconcernpossiblyrelatedtolong-termcorticosteroidusewerereportedby4.8%of

thepatientsintheDovobetointmentgroup,2.8%intheDovobet/Dovonexalternatinggroupand2.9%inthe

Dovonexgroup.

AdrenalresponsetoACTHwasdeterminedbymeasuringserumcortisollevelsinpatientswithbothextensivescalp

andbodypsoriasis,usingupto106gperweekcombinedDovobetgelandDovobetointment.Aborderlinedecreasein

cortisolresponseat30minutespostACTHchallengewasseenin5of32patients(15.6%)after4weeksoftreatment

and2of11patients(18.2%)whocontinuedtreatmentuntil8weeks.Inallcases,theserumcortisollevelswerenormal

at60minutespostACTHchallenge.Therewasnoevidenceofchangeofcalciummetabolismobservedinthese

patients.WithregardtoHPAsuppression,therefore,thisstudyshowssomeevidencethatveryhighdosesofDovobet

gelandointmentmayhaveaweakeffectontheHPAaxis.

5.2Pharmacokineticproperties

Clinicalstudieswithradiolabelledointmentindicatethatthesystemicabsorptionofcalcipotriolandbetamethasone

fromDovobetointmentislessthan1%ofthedose(2.5g)whenappliedtonormalskin(625cm

)for12hours.Applicationtopsoriasisplaquesandunderocclusivedressingsmayincreasetheabsorptionoftopical

corticosteroids.Absorptionthroughdamagedskinisapprox24%.

Followingsystemicexposure,bothactiveingredients–calcipotriolandbetamethasonedipropionatearerapidlyand

extensivelymetabolised.Proteinbindingisapprox64%.Plasmaeliminationhalf-lifeafterintravenousapplicationis5-

6hours.Duetotheformationofadepotintheskineliminationafterdermalapplicationisinorderofdays.

Betamethasoneismetabolisedespeciallyintheliver,butalsointhekidneystoglucuronideandsulphateesters.The

mainrouteofexcretionofcalcipotriolisviafaeces(ratsandminipigs)andforbetamethasonedipropionateitisvia

urine(ratsandmice).Inrats,tissuedistributionstudieswithradiolabelledcalcipotriolandbetamethasonedipropionate,

respectively,showedthatthekidneyandliverhadthehighestlevelofradioactivity.

Calcipotriolandbetamethasonedipropionatewerebelowthelowerlimitofquantificationinallbloodsamplesof34

patientstreated,for4or8weekswithbothDovobetgelandDovobetointment,forextensivepsoriasisinvolvingthe

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someofthepatients.

5.3Preclinicalsafetydata

Studiesofcorticosteroidsinanimalshaveshownreproductivetoxicity(cleftpalate,skeletalmalformations).In

reproductiontoxicitystudieswithlong-termoraladministrationofcorticosteroidstoratsprolongedgestationand

prolongedanddifficultlabourwasdetected.Moreoverreductioninoffspringsurvival,inbodyweightandbodyweight

gainwasobserved.Therewasnoimpairmentoffertility.Therelevanceforhumansisunknown.

Adermalcarcinogenicitystudyinmicerevealednospecialhazardtohumans.

Photo(co)carcinogenicitystudiesinmicesuggestthatcalcipotriolmayenhancetheeffectofUVRtoinduceskin

tumours.

Nocarcinogenicityorphotocarcinogenicitystudieshavebeenperformedwithbetamethasonedipropionate.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Liquidparaffin

Polyoxypropylene-15-stearylether

-tocopherol

Whitesoftparaffin

Butylhydroxytoluene(E321)

6.2Incompatibilities

Nottobemixedwithothermedicinalproducts.

6.3Shelflife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

Aluminium/epoxyphenoltubeswithpolyethylenescrewcap.

Tubesizes:60and120g.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7PARALLELPRODUCTAUTHORISATIONHOLDER

IPSHealthcareLimited

SterlingHouse

501MiddletonRoad

Chadderton

Oldham

Lancashire

OL99LY

UnitedKingdom

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1659/18/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:8thOctober2010

10DATEOFREVISIONOFTHETEXT

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